Developmental expression of IL-12Rβ2 on murine naive neonatal T cells counters the upregulation of IL-13Rα1 on primary Th1 cells and balances immunity in the newborn

Christine M. Hoeman, Mermagya Dhakal, Adam A. Zaghouani, Jason A. Cascio, Xiaoxiao Wan, Marie Therese Khairallah, Weirong Chen, Habib Zaghouani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Upon exposure to Ag on the day of birth, neonatal mice mount balanced primary Th1 and Th2 responses, with the former displaying upregulated IL-13Rα1 expression. This chain associates with IL-4Rα to form a heteroreceptor (IL-4Rα/IL-13Rα1) that marks the Th1 cells for death by IL-4 produced by Th2 cells during rechallenge with Ag, hence the Th2 bias of murine neonatal immunity. The upregulation of IL-13Rα1 on neonatal Th1 cells was due to the paucity of IL-12 in the neonatal environment. In this study, we show that by day 8 after birth, naive splenic T cells are no longer susceptible to IL-13Rα1 upregulation even when exposed to Ag within the neonatal environment. Furthermore, during the 8-d lapse, the naive splenic T cells spontaneously and progressively upregulate the IL-12Rβ2 chain, perhaps due to colonization by commensals, which induce production of IL-12 by cells of the innate immune system such as dendritic cells. In fact, mature T cells from the thymus, a sterile environment not accessible to microbes, did not upregulate IL-12Rβ2 and were unable to counter IL-13Rα1 upregulation. Finally, the 8-d naive T cells were able to differentiate into Th1 cells even independently of IL-12 but required the cytokine to counter upregulation of IL-13Rα1. Thus, in neonatal mice, IL-12, which accumulates in the environment progressively, uses IL-12Rβ2 to counter IL-13Rα1 expression in addition to promoting Th1 differentiation.

Original languageEnglish (US)
Pages (from-to)6155-6163
Number of pages9
JournalJournal of Immunology
Volume190
Issue number12
DOIs
StatePublished - Jun 15 2013

ASJC Scopus subject areas

  • Immunology

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